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Metschl, S., Bruder, L., Paloschi, V., Jakob, K., Reutersberg, B., Reeps, C., Maegdefessel, L., Gee, M.W., Eckstein, H.-H., Pelisek, J.
Changes of endocan and dermatan sulfate are associated with biomechanical properties of abdominal aortic wall during aneurysm expansion and rupture
Background and aims: The study aimed to assess the potential of proteoglycans (PG) and collagens as serological biomarkers in the abdominal aortic aneurysm (AAA). Furthermore, we investigated the underlying mechano-biological interactions and signaling pathways. Methods: Tissue and serum samples from patients with ruptured AAA (rAAA, n=29), elective AAA (eAAA, n=78), and healthy individuals (n=8) were evaluated by histology, immunohistochemistry and Enzyme-linked Immunosorbent Assay (ELISA), mechanical properties were assessed by tensile tests. Regulatory pathways were determined by membrane-based sandwich immunoassay. Results: In AAA samples, collagen type I and III (Col1, Col3), chondroitin sulfate (CS), and dermatan sulfate (DS) were significantly increased compared to controls (3.0-, 3.2-, 1.3-, and 53-fold; p<0.01). Col1 and endocan were also elevated in the serum of AAA patients (3.6- and 6.0-fold; p<0.01), while DS was significantly decreased (2.5-fold; p<0.01). Histological scoring showed increased total PGs and focal accumulation in rAAA compared to eAAA. Tissue β-stiffness was higher in rAAA compared to eAAA (2.0-fold, p=0.02). Serum Col1 correlated with maximum tensile force and failure tension (r=0.448 and 0.333; p<0.01 and =0.02), tissue endocan correlated with α-stiffness (r=0.340; p<0.01). Signaling pathways in AAA were associated with ECM synthesis and VSMC proliferation. In particular, Src family kinases, PDGF- and EGF-related proteins seem to be involved. Conclusions: Our findings reveal a structural association between collagen and PGs and their response to changes in mechanical loads in AAA. Particularly Col1 and endocan reflect the mechano-biological conditions of the aortic wall also in the patient’s serum and might serve for AAA risk stratification.
Journal title:
Thrombosis and Haemostasis
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